This proposal seeks support of a search for a genetic marker of essential hypertension in man. We have recently observed that the maximum rate of sodium-dependent lithium transport (Na-Li transport) in the erythrocytes of patients with essential hypertension is 2-3 times faster than in normal human subjects. Since differences in Na-Li transport between individuals are, at least in part, inherited, it is possible that increased Na-Li transport is an expression of a genetic difference between persons suffering from essential hypertension and others. We intend to explore this possibility by 1) establishing the extent of correlation of increased Na-Li transport with different forms of hypertension, 2) studying the inheritance of Na-Li transport in families of individuals with various forms of hypertension and in normotensive subjects, 3) elucidating the mechanism of increased Na-Li transport in red cells of hypertensive patients, 4) exploring the relation of increased Na-Li transport to the pathogenesis of hypertension. We hope that these investigations will lead to improvements in the clinical management of essential hypertension by finding better ways to detect genetic predisposition toward the syndrome prior to its onset and by devising more effective therapies based on a more thorough understanding of the pathogenesis of the disorder.